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Departments of ¹ Veterinary Physiology and Pharmacology and ² Biochemistry and Biophysics,, Texas A & M University, College Station, Texas 77843-4466, USA ³ The Institute of Biosciences and Technology,, Texas A & M University Health Science Center, 2121 West Holcombe Boulevard, Houston, Texas 77030, USA

(Correspondence should be addressed to S Safe; Email: ssafe{at}cvm.tamu.edu)

The authors have nothing to disclose.

Deletion analysis of several 17ß-estradiol (E₂)-responsive genes have identified GC-rich sites that are associated with hormone-induced transactivation in MCF-7 breast cancer cells. However, the role of individual specificity proteins (Sps) in mediating hormone-induced gene expression has not been unequivocally determined. In transient transfection studies using E₂-responsive GC-rich promoters from the E₂F1, carbamoylphosphate synthetase/aspartate transcarbamylase/dihydroorotase (CAD), and retinoic acid receptor (RAR) genes, RNA interference using small inhibitory RNAs for Sp1 (iSp1), Sp3 (iSp3), and Sp4 (iSp4) decreased both basal and E₂-induced transactivation. The contributions of individual Sp proteins to basal and E₂-induced activity were promoter dependent. iSp1, iSp3, and iSp4 also significantly inhibited hormonal induction of E₂F1, CAD, and RAR mRNA levels; however, the enhanced inhibitory effects of the latter two small inhibitory RNAs suggest that Sp3 and Sp4 play a major role in estrogen receptor /Sp-mediated gene expression in MCF-7 cells.

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				G. Chadalapaka, I. Jutooru, S. Chintharlapalli, S. Papineni, R. Smith III, X. Li, and S. Safe Curcumin Decreases Specificity Protein Expression in Bladder Cancer Cells Cancer Res., July 1, 2008; 68(13): 5345 - 5354. [Abstract] [Full Text] [PDF]